On November 16, 2017 X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 inhibitor drugs to improve immune cell trafficking to treat cancer and rare diseases, reported the successful completion of a $27 million Series B financing (Press release, X4 Pharmaceuticals, NOV 16, 2017, View Source [SID1234522108]). Proceeds from the financing will be used to advance X4’s two lead drug candidates in clinical efficacy studies in immuno-oncology and a pivotal study in WHIM syndrome, a rare primary immunodeficiency disease. X4’s novel therapeutics are directed against the CXCR4 pathway to correct the trafficking of key immune cells that regulate healthy immune surveillance throughout the body.

"We are incredibly pleased to have the support of Cormorant Asset Management and additional new and existing investors to support our mission of bringing innovative treatments to patients with cancer and rare diseases," said Paula Ragan, PhD, President and CEO of X4. "We are now in a strong position to advance our lead candidate in WHIM syndrome into a pivotal study in 2018 and to advance our proof of concept studies in oncology. This financing recognizes the progress we have made as well as the important milestones that lie ahead in 2018."

"Having been an investor in the earliest stages of X4, we have witnessed the strong progress the company has made and the impact these treatments are having for patients," said Bihua Chen, CEO and Portfolio Manager, Cormorant Asset Management. "X4 has built a differentiated approach rooted in strong science and clear regulatory pathways. We are pleased to support X4’s continuing work in developing and commercializing innovative therapies for primary immunodeficiencies and cancer."

In the two years since X4 launched in 2015, the company has rapidly entered clinical studies with lead programs for two different diseases: as an immuno-oncology agent for solid tumors and as a treatment for the rare disease WHIM syndrome. The company’s oral, small molecule drug candidates inhibit the binding of chemokine CXCL12 to C-X-C receptor type 4 (CXCR4), a receptor-ligand pair that plays an essential role in normal immune surveillance. X4P-001-IO has demonstrated encouraging results in Phase 1/2 testing in refractory clear cell renal cell carcinoma, as well as in melanoma where results support activation of the immune system. In addition, X4P-001-RD has demonstrated initial proof-of-concept in the Phase 2 portion of an on-going Phase 2/3 study in patients with WHIM syndrome.

About Renal Cell Carcinoma

Kidney cancer is among the ten most common cancers in both men and women with more than 60,000 new diagnoses each year in the United States.1 Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, and advanced ccRCC accounts for approximately 20% of the patient population. Therapies for advanced ccRCC include immunotherapies, mammalian target of rapamycin (mTOR) kinase inhibitors, and angiogenesis inhibitors, such as vascular endothelial growth factor (VEGF) inhibitors.2 There continue to be unmet medical needs with advanced ccRCC because durable responses remain a serious clinical challenge for patients with advanced disease.

About WHIM Syndrome

WHIM syndrome is a primary immunodeficiency disease ("PID") caused by genetic mutations in the CXCR4 receptor gene resulting in susceptibility to certain types of infections. WHIM is an abbreviation for the characteristic clinical symptoms of the syndrome: Warts, Hypogammaglobulinemia, Infections, and Myelokathexis. Within the overall category of primary immunodeficiencies, there are between 15,000 and 100,000 patients in the US that are classified with PID of unknown origin — of which WHIM is one.3,4,5 WHIM syndrome is a rare disorder and the precise prevalence or incidence of patients that have the genetic mutation responsible for WHIM syndrome is unknown. Because patients are highly susceptible to infections, WHIM syndrome is associated with significant morbidity beginning in early childhood and continuing throughout life. Current therapy is limited to treatment of acute infections with antibiotics or prevention through the use of intravenous immunoglobulin or G-CSF. There is no approved therapy for the treatment of WHIM syndrome.

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On September 16, 2017 Stemline Therapeutics, Inc. (Nasdaq:STML), a clinical-stage biopharmaceutical company developing novel therapeutics for difficult to treat cancers, reported that data from the Phase 2 trial of SL-701 in patients with second-line glioblastoma (GBM) were selected for oral presentation at the 22nd Annual Meeting of the Society of Neuro-Oncology (SNO) being held November 16-19, 2017 in San Francisco, CA (Press release, Stemline Therapeutics, NOV 16, 2017, View Source [SID1234522107]).

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David A. Reardon, M.D., lead investigator of the study and presenting author, commented, "SL-701 is exhibiting very encouraging clinical activity, including long-term survivors, as both a single agent and in combination with bevacizumab in a relapsed GBM patient population. Notably, we are also witnessing evidence of a robust target-specific CD8+ T-cell response tracking with clinical benefit – a very exciting development and confirmation of the drug’s immune mechanism of action. Given the positive results seen here, combined with a high unmet medical need in GBM, I will be working closely with Stemline to develop a rational, registrational path forward for SL-701."

Details on the presentation are as follows:

Title:
Phase 2 Trial of SL-701, a novel immunotherapy comprised of synthetic short peptides against GBM targets IL-13Rα2, EphA2, and survivin, in adults with second-line recurrent GBM
Presenter: David Reardon, MD; Dana-Farber Cancer Institute
Abstract: ATIM-10
Date/Time: Sunday, November 19, 2017 – 10:45-10:55 AM PT

A copy of the oral presentation will be available on the Stemline website (www.stemline.com), under the Scientific Presentations tab, following the SNO presentation.

Istari Oncology’s second technology platform consists of a series of ADCs for a variety of oncology targets (Company Web Page, Istari Oncology, NOV 15, 2017, View Source [SID1234522093]). These select, highly specific, monoclonal antibodies are presently conjugated with PE-38 toxin to maximize the killing effect.
We believe our platform overcomes some of the challenges associated with other ADCs because it is based on genetic linkage, which provides more stability than chemical linkers, making it is easier to manufacture. The FDA granted our ADC conjugate, D2C7-IT, Orphan Drug designation in 2016.
Beyond the various PE-38 toxins, our technology could be linked with other therapeutic agents for different targets. Toxins used in construction of immunotoxins are typically derived from bacteria, fungi, and plants. These agents and linkers potentially provide another platform for additional pipeline therapeutics. Possible tumor targets include solid, nonlymphoid tumors.

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On November 15, 2017 Invitae Corporation (NYSE: NVTA), one of the fastest growing genetic information companies, reported it has completed its acquisition of CombiMatrix, which specializes in providing genetic information for prenatal diagnosis, miscarriage analysis and diagnosis of pediatric developmental disorders, establishing Invitae as a new leader in family and reproductive genetic health services (Press release, CombiMatrix, NOV 15, 2017, View Source [SID1234522094]).

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Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. www.invitae.com (PRNewsFoto/Invitae Corporation)

"With the addition of CombiMatrix to Invitae, we have completed our entry into prenatal and perinatal genetics, currently the second-largest category of genetic testing services. Our integrated offering will build on the expertise and technologies developed by CombiMatrix to offer customers the most comprehensive offering from a single provider in the category," said Sean George, chief executive officer of Invitae. "Invitae’s platform now delivers comprehensive genetic information services that support the use of genetics in mainstream medical care throughout all stages of life."

CombiMatrix leverages cytogenomic and cytogenetic technologies such as single nucleotide polymorphism chromosomal microarray analysis and next generation sequencing, supported by long-standing expertise in technically challenging sample types, to provide in-depth answers for patients and clinicians addressing complex reproductive health questions.

"Access to actionable genetic information is essential for monitoring pregnancies, particularly for women going through IVF or facing recurrent miscarriages," said Robert Nussbaum, MD, chief medical officer of Invitae. "Our integrated platform and world-class expertise can provide genetic information that helps women and their clinicians with some of the most important decisions of their lives today, even as we continue to advance the understanding of the role genetics plays in having healthy pregnancies."

In connection with the closing, Invitae issued approximately $21.2 million in shares of its common stock to former CombiMatrix securityholders, or approximately 2.7 million shares. Together with the approximately 1.7 million shares of Invitae common stock underlying CombiMatrix Series F warrants assumed in the Merger, the transaction has a total enterprise value of approximately $34.9 million.

The acquisition of CombiMatrix complements Invitae’s recent acquisition of another reproductive genetics company, Good Start Genetics, to establish a category-leading menu with the breadth and depth needed to provide comprehensive support for women, their partners and clinicians to use genetic information when considering their reproductive health options, from carrier screening to preimplantation genetic screening and diagnosis to newborn diagnostics.

Transaction Details

At the closing of the Merger, Invitae issued shares of its common stock to (i) CombiMatrix’s common stockholders, at an exchange ratio of 0.8692 of a share of Invitae common stock (the "Merger Exchange Ratio") for each share of CombiMatrix common stock outstanding immediately prior to the Merger, (ii) CombiMatrix’s Series F preferred stockholders, at the Merger Exchange Ratio for each share of CombiMatrix common stock underlying Series F preferred stock outstanding immediately prior to the Merger, (iii) holders of outstanding and unexercised in-the-money CombiMatrix stock options, which were fully accelerated to the extent of any applicable vesting period and converted into the right to receive a number of shares of Invitae common stock adjusted for the Merger Exchange Ratio and reduced by the aggregate exercise price, and (iv) holders of outstanding and unsettled CombiMatrix restricted stock units ("RSUs"), which were fully accelerated to the extent of any applicable vesting period and converted into the right to receive a number of shares of Invitae common stock adjusted for the Merger Exchange Ratio. No fractional shares were issued in connection with the Merger and Invitae will pay cash in lieu of any such fractional shares. The Merger Exchange Ratio was determined through arm’s-length negotiations between Invitae and CombiMatrix.

In addition, at the closing of the Merger, (a) all outstanding and unexercised out-of-the money CombiMatrix stock options were cancelled and terminated without the right to receive any consideration, (b) all CombiMatrix Series D Warrants and Series F Warrants outstanding and unexercised immediately prior to the closing of the Merger were assumed by Invitae and converted into warrants to purchase the number of shares of Invitae common stock determined by multiplying the number of shares of CombiMatrix common stock subject to such warrants by the Merger Exchange Ratio, and with the exercise price adjusted by dividing the per share exercise price of the CombiMatrix common stock subject to such warrants by the Merger Exchange Ratio, and (c) certain entitlements under CombiMatrix’s executive compensation transaction bonus plan (the "Transaction Bonus Plan") were paid in shares of Invitae common stock or RSUs to be settled in shares of Invitae common stock. All outstanding and unexercised CombiMatrix Series A, Series B, Series C, Series E, and PIPE warrants were repurchased by CombiMatrix prior to closing pursuant to that certain CombiMatrix Common Stock Purchase Warrants Repurchase Agreement dated July 11, 2016.

Invitae’s previously announced offer to exchange each outstanding Series F warrant (the "CombiMatrix Series F warrants") to acquire one share of common stock of CombiMatrix for 0.3056 of a share of Invitae common stock (the "Exchange Offer") expired at 12:00 midnight (one minute after 11:59 p.m.), New York City time, on November 13, 2017. Because the minimum tender condition of 90% was not achieved in the Exchange Offer, Invitae did not accept any of the CombiMatrix Series F warrants that were tendered in the Exchange Offer prior to its expiration. Accordingly, any CombiMatrix Series F warrants that were tendered will be promptly returned to the holder by the exchange agent.

Invitae issued an aggregate of 2,726,324 shares of its common stock and 214,976 RSUs in connection with the Merger (including shares and RSUs issued pursuant to the Transaction Bonus Plan). Immediately after the Merger, (i) there were approximately 52.9 million shares of Invitae common outstanding, (ii) the former CombiMatrix securityholders and executives owned approximately 8.6% of the fully-diluted common stock of the combined company, and (iii) Invitae securityholders, whose shares of Invitae capital stock remain outstanding after the Merger, owned approximately 91.4% of the fully-diluted common stock of the combined company.

Upon completion of the Merger, CombiMatrix became a wholly owned subsidiary of Invitae. As a result, the CombiMatrix common stock and Series F warrants will cease trading on the Nasdaq Capital Market and will be delisted.

About Invitae’s Family and Reproductive Health Genetic Services

Invitae’s reproductive genetics products, which include CombiPGS, CombiPGD and CombiSNP from CombiMatrix and Good Start Genetics’ GeneVu, EmbryVu and VeriYou, provide affordable and accessible genetic information to help people have healthy families. Good Start Genetics became part of Invitae in August 2017.

On November 15, 2017 Arvinas LLC, a private biotechnology company creating a new class of drugs based on protein degradation, reported it has expanded its ongoing license agreement with Genentech, a member of the Roche Group, for the development of new therapeutics using Arvinas’ novel PROTAC technology (Press release, Arvinas, NOV 15, 2017, View Source [SID1234558785]). The multi-year strategic license agreement, initiated in October 2015, will encompass additional disease targets and expand the collaboration.

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Under the revised terms of the agreement, Arvinas is eligible to receive development and commercialization milestone payments in excess of $650 million based on achievement of certain predetermined milestones. In addition, Arvinas is eligible to receive tiered-royalties on sales of products resulting from the license agreement. Full financial terms have not been disclosed.

"Genentech’s decision to expand our original agreement to include additional disease targets shows the promise seen in our first two years together and further supports our targeted protein degradation platform as a novel drug modality to treat a broad array of diseases," said John Houston, Ph.D., President and Chief Executive Officer of Arvinas. "This expansion also supports our initial decision to work with Genentech in 2015 and we look forward to this growing collaboration."

The PROTAC Platform offers potential improvements over traditional small molecule inhibitors using the ubiquitin and proteasome system within a cell to degrade disease causing proteins. By removing target proteins directly rather than inhibiting them, PROTACs can provide multiple advantages over small molecule inhibitors, which can require high systemic exposure to achieve sufficient inhibition, often resulting in toxic side effects and eventual drug resistance.